New Susceptibility and Resistance HLA-DP Alleles to HBV-Related Diseases Identified by a Trans-Ethnic Association Study in Asia

被引：35

作者：

Nishida, Nao ^{[1
,2
]}

Sawai, Hiromi ^{[2
]}

Kashiwase, Koichi ^{[3
]}

Minami, Mutsuhiko ^{[3
]}

Sugiyama, Masaya ^{[1
]}

Seto, Wai-Kay ^{[4
]}

Yuen, Man-Fung ^{[4
]}

Posuwan, Nawarat ^{[5
]}

Poovorawan, Yong ^{[5
]}

Ahn, Sang Hoon ^{[6
]}

Han, Kwang-Hyub ^{[6
]}

Matsuura, Kentaro ^{[7
,8
]}

Tanaka, Yasuhito ^{[7
,8
]}

Kurosaki, Masayuki ^{[9
]}

Asahina, Yasuhiro ^{[10
,11
]}

Izumi, Namiki ^{[9
]}

Kang, Jong-Hon ^{[12
]}

Hige, Shuhei ^{[13
]}

Ide, Tatsuya ^{[14
]}

Yamamoto, Kazuhide ^{[15
]}

Sakaida, Isao ^{[16
]}

Murawaki, Yoshikazu ^{[17
]}

Itoh, Yoshito ^{[18
]}

Tamori, Akihiro ^{[19
]}

Orito, Etsuro ^{[20
]}

Hiasa, Yoichi ^{[21
]}

Honda, Masao ^{[22
]}

Kaneko, Shuichi ^{[22
]}

Mita, Eiji ^{[23
]}

Suzuki, Kazuyuki ^{[24
]}

Hino, Keisuke ^{[25
]}

Tanaka, Eiji ^{[26
]}

Mochida, Satoshi ^{[27
]}

Watanabe, Masaaki ^{[28
]}

Eguchi, Yuichiro ^{[29
]}

Masaki, Naohiko ^{[1
]}

Murata, Kazumoto ^{[1
]}

Korenaga, Masaaki ^{[1
]}

Mawatari, Yoriko ^{[1
]}

Ohashi, Jun ^{[30
]}

Kawashima, Minae ^{[2
]}

Tokunaga, Katsushi ^{[2
]}

Mizokami, Masashi ^{[1
]}

机构：

[1] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Ichikawa, Chiba, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Human Genet, Bunkyo Ku, Tokyo, Japan

[3] Japanese Red Cross Kanto Koshinetsu Block Blood C, HLA Lab, Koutou Ku, Tokyo, Japan

[4] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China

[5] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand

[6] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea

[7] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan

[8] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi, Japan

[9] Musashino Red Cross Hosp, Div Gastroenterol & Hepatol, Musashino, Tokyo, Japan

[10] Tokyo Med & Dent Univ, Dept Liver Dis Control, Bunkyo Ku, Tokyo, Japan

[11] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Bunkyo Ku, Tokyo, Japan

[12] Teine Keijinkai Hosp, Dept Internal Med, Sapporo, Hokkaido, Japan

[13] Hokkaido Univ, Grad Sch Med, Dept Internal Med, Sapporo, Hokkaido, Japan

[14] Kurume Univ, Sch Med, Dept Med, Div Gastroenterol, Kurume, Fukuoka 830, Japan

[15] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol, Okayama, Japan

[16] Yamaguchi Univ, Grad Sch Med, Ube, Yamaguchi 755, Japan

[17] Tottori Univ, Fac Med, Tottori 680, Japan

[18] Kyoto Prefectural Univ Med, Kyoto, Japan

[19] Osaka City Univ, Grad Sch Med, Dept Hepatol, Osaka 558, Japan

[20] Nagoya Daini Red Cross Hosp, Dept Gastroenterol, Nagoya, Aichi, Japan

[21] Ehime Univ, Dept Gastroenterol & Metabol, Grad Sch Med, Toon, Ehime, Japan

[22] Kanazawa Univ, Grad Sch Med, Dept Gastroenterol, Kanazawa, Ishikawa, Japan

[23] Osaka Natl Hosp, Natl Hosp Org, Dept Gastroenterol & Hepatol, Osaka, Japan

[24] Iwate Med Univ, Dept Internal Med, Div Gastroenterol & Hepatol, Morioka, Iwate 020, Japan

[25] Kawasaki Med Coll, Div Hepatol & Pancreatol, Kurashiki, Okayama, Japan

[26] Shinshu Univ, Sch Med, Dept Med, Matsumoto, Nagano 390, Japan

[27] Saitama Med Univ, Div Gastroenterol & Hepatol, Iruma, Saitama, Japan

[28] Kitasato Univ, Sch Med, Dept Gastroenterol, Sagamihara, Kanagawa 228, Japan

[29] Saga Med Sch, Dept Internal Med, Saga, Japan

[30] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan

来源：

PLOS ONE | 2014年 / 9卷 / 02期

关键词：

GENOME-WIDE ASSOCIATION; CHRONIC HEPATITIS-B; VIRUS CLEARANCE; POLYMORPHISM; VARIANTS; LOCUS;

D O I：

10.1371/journal.pone.0086449

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36 x 10(-6); OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22 x 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 x 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.

引用

页数：7

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